Department of Biosystems, Science and Engineering (D-BSSE), ETH Zurich, Mattenstraße 26, 4058 Basel, Switzerland.
Swiss Institute of Bioinformatics (SIB), Mattenstraße 26, 4058 Basel, Switzerland.
Development. 2021 May 1;148(9). doi: 10.1242/dev.194209. Epub 2021 May 4.
During lung development, epithelial branches expand preferentially in a longitudinal direction. This bias in outgrowth has been linked to a bias in cell shape and in the cell division plane. How this bias arises is unknown. Here, we show that biased epithelial outgrowth occurs independent of the surrounding mesenchyme, of preferential turnover of the extracellular matrix at the bud tips and of FGF signalling. There is also no evidence for actin-rich filopodia at the bud tips. Rather, we find epithelial tubes to be collapsed during early lung and kidney development, and we observe fluid flow in the narrow tubes. By simulating the measured fluid flow inside segmented narrow epithelial tubes, we show that the shear stress levels on the apical surface are sufficient to explain the reported bias in cell shape and outgrowth. We use a cell-based vertex model to confirm that apical shear forces, unlike constricting forces, can give rise to both the observed bias in cell shapes and tube elongation. We conclude that shear stress may be a more general driver of biased tube elongation beyond its established role in angiogenesis. This article has an associated 'The people behind the papers' interview.
在肺发育过程中,上皮分支优先沿纵向方向扩展。这种生长的偏差与细胞形状和细胞分裂平面的偏差有关。这种偏差是如何产生的尚不清楚。在这里,我们表明,偏向性的上皮生长发生于周围间质之外,在芽尖处细胞外基质的优先周转以及 FGF 信号的影响之外。芽尖处也没有富含肌动蛋白的丝状伪足的证据。相反,我们发现肺和肾发育早期上皮管塌陷,并且我们观察到狭窄管内的流体流动。通过模拟分段狭窄上皮管内测量的流体流动,我们表明,在顶端表面上的剪切应力水平足以解释报告的细胞形状和生长的偏差。我们使用基于细胞的顶点模型来确认,与收缩力不同,顶端剪切力可以导致观察到的细胞形状和管伸长的偏差。我们得出结论,剪切应力可能是偏向性管伸长的更普遍驱动因素,而不仅仅是其在血管生成中的既定作用。本文有一个相关的“论文背后的人物”采访。